CN106404953B - A kind of quality determining method of penicillin skin test freeze dried powder - Google Patents
A kind of quality determining method of penicillin skin test freeze dried powder Download PDFInfo
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- CN106404953B CN106404953B CN201610797234.2A CN201610797234A CN106404953B CN 106404953 B CN106404953 B CN 106404953B CN 201610797234 A CN201610797234 A CN 201610797234A CN 106404953 B CN106404953 B CN 106404953B
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- 238000012360 testing method Methods 0.000 title claims abstract description 88
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 title claims abstract description 70
- 229930182555 Penicillin Natural products 0.000 title claims abstract description 56
- 239000000843 powder Substances 0.000 title claims abstract description 53
- 229940049954 penicillin Drugs 0.000 title claims abstract description 52
- 238000000034 method Methods 0.000 title claims abstract description 45
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 66
- 239000000243 solution Substances 0.000 claims abstract description 38
- 239000012085 test solution Substances 0.000 claims abstract description 36
- FCPVYOBCFFNJFS-LQDWTQKMSA-M benzylpenicillin sodium Chemical compound [Na+].N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 FCPVYOBCFFNJFS-LQDWTQKMSA-M 0.000 claims abstract description 31
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 13
- 239000011521 glass Substances 0.000 claims abstract description 10
- 239000000706 filtrate Substances 0.000 claims abstract description 5
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 238000001514 detection method Methods 0.000 claims description 36
- 239000013558 reference substance Substances 0.000 claims description 29
- 238000002360 preparation method Methods 0.000 claims description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000007788 liquid Substances 0.000 claims description 11
- 238000010829 isocratic elution Methods 0.000 claims description 9
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 5
- 229930195725 Mannitol Natural products 0.000 claims description 5
- 239000008101 lactose Substances 0.000 claims description 5
- 239000000594 mannitol Substances 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- 230000005526 G1 to G0 transition Effects 0.000 claims description 4
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 239000000463 material Substances 0.000 abstract description 7
- 238000003908 quality control method Methods 0.000 abstract description 4
- 230000002349 favourable effect Effects 0.000 abstract description 2
- 239000003814 drug Substances 0.000 description 23
- 239000007924 injection Substances 0.000 description 19
- 238000002347 injection Methods 0.000 description 19
- 229940079593 drug Drugs 0.000 description 15
- 239000003153 chemical reaction reagent Substances 0.000 description 10
- 229940056360 penicillin g Drugs 0.000 description 10
- 238000003556 assay Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
- 238000010521 absorption reaction Methods 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 235000019371 penicillin G benzathine Nutrition 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- 239000012535 impurity Substances 0.000 description 7
- 230000014759 maintenance of location Effects 0.000 description 5
- 238000012856 packing Methods 0.000 description 5
- 150000002960 penicillins Chemical class 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012362 glacial acetic acid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- 239000012530 fluid Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 238000007689 inspection Methods 0.000 description 3
- 238000004811 liquid chromatography Methods 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000012372 quality testing Methods 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- WXYIONYJZVWSIJ-UHFFFAOYSA-N acetonitrile;methanol;hydrate Chemical group O.OC.CC#N WXYIONYJZVWSIJ-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000002052 anaphylactic effect Effects 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 238000000711 polarimetry Methods 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- OPEGYZAATHKDEM-HCWXCVPCSA-N (2r,4s)-2-[(r)-carboxy(formamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC1(C)S[C@H]([C@H](NC=O)C(O)=O)N[C@H]1C(O)=O OPEGYZAATHKDEM-HCWXCVPCSA-N 0.000 description 1
- DWNBOPVKNPVNQG-LURJTMIESA-N (2s)-4-hydroxy-2-(propylamino)butanoic acid Chemical compound CCCN[C@H](C(O)=O)CCO DWNBOPVKNPVNQG-LURJTMIESA-N 0.000 description 1
- IJVLVRYLIMQVDD-UHFFFAOYSA-N 1,3-thiazole-2-carboxylic acid Chemical class OC(=O)C1=NC=CS1 IJVLVRYLIMQVDD-UHFFFAOYSA-N 0.000 description 1
- 206010002198 Anaphylactic reaction Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010013700 Drug hypersensitivity Diseases 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 1
- 229960001931 ampicillin sodium Drugs 0.000 description 1
- 230000036783 anaphylactic response Effects 0.000 description 1
- 208000003455 anaphylaxis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229940121657 clinical drug Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- QGBSISYHAICWAH-UHFFFAOYSA-N dicyandiamide Chemical compound NC(N)=NC#N QGBSISYHAICWAH-UHFFFAOYSA-N 0.000 description 1
- FWRNIJIOFYDBES-ZQDFAFASSA-L disodium;(2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-sulfonatoacetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].[Na+].C1([C@H](C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)S([O-])(=O)=O)=CC=CC=C1 FWRNIJIOFYDBES-ZQDFAFASSA-L 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011067 equilibration Methods 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000010977 jade Substances 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 238000012417 linear regression Methods 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000012982 microporous membrane Substances 0.000 description 1
- 229910000403 monosodium phosphate Inorganic materials 0.000 description 1
- 235000019799 monosodium phosphate Nutrition 0.000 description 1
- 230000000474 nursing effect Effects 0.000 description 1
- YTJSFYQNRXLOIC-UHFFFAOYSA-N octadecylsilane Chemical compound CCCCCCCCCCCCCCCCCC[SiH3] YTJSFYQNRXLOIC-UHFFFAOYSA-N 0.000 description 1
- 238000005457 optimization Methods 0.000 description 1
- 229940124585 oral penicillin Drugs 0.000 description 1
- VDUVBBMAXXHEQP-SLINCCQESA-M oxacillin sodium Chemical compound [Na+].N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C([O-])=O)=O)C(=O)C1=C(C)ON=C1C1=CC=CC=C1 VDUVBBMAXXHEQP-SLINCCQESA-M 0.000 description 1
- 201000005354 penicillin allergy Diseases 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- QGPGUZIKJKOKRF-UHFFFAOYSA-M potassium;acetonitrile;dihydrogen phosphate Chemical compound [K+].CC#N.OP(O)([O-])=O QGPGUZIKJKOKRF-UHFFFAOYSA-M 0.000 description 1
- NHOXRBDMOTVJBL-UHFFFAOYSA-M potassium;dihydrogen phosphate;methanol Chemical compound [K+].OC.OP(O)([O-])=O NHOXRBDMOTVJBL-UHFFFAOYSA-M 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000002798 spectrophotometry method Methods 0.000 description 1
- 230000006641 stabilisation Effects 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 238000011105 stabilization Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 229910021642 ultra pure water Inorganic materials 0.000 description 1
- 239000012498 ultrapure water Substances 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention discloses a kind of quality determining methods of penicillin skin test freeze dried powder, include the following steps: that (1) precision weighs Benzylpenicillin sodium salt standard items 0.02g, constant volume is dissolved with acetonitrile, it is miscible, it is made into the solution that concentration is 0.2~2mg/ml, it is stored in Brown Glass Brown glass bottles and jars only, and places and save under the conditions of 2~8 DEG C;(2) penicillin skin test freeze dried powder 0.2g is taken, it is accurately weighed, it is placed in measuring bottle in right amount, acetonitrile is added to dissolve fine powder, be settled to 2ml, shake up, filter, take subsequent filtrate as test solution;(3) it is detected using high performance liquid chromatography.Benzylpenicillin sodium salt skin test freeze dried powder quality determining method provided by the invention, specificity is strong, favorable reproducibility, it is versatile, Benzylpenicillin sodium salt main peak and auxiliary material peak can be efficiently separated, testing result is accurate, substantially increases the quality control level to penicillin skin test freeze dried powder, it is ensured that the safety of clinical application.
Description
Technical field
The present invention relates to pharmacy and Pharmaceutical Analysis technical field, and in particular to a kind of quality of penicillin skin test freeze dried powder
Detection method.
Background technique
Penicillins (Penicilins) drug is the general name of the interior phthalein amine antibiotic of a kind of β-, because its efficient, low toxicity is
Most popular one of drug is applied on clinical medicine at present, although penicillin medicine itself does not have very virulent property to body,
But easily cause drug anaphylaxis, be all kinds of allergic drugs most.The reason of penicillin allergy mainly penicillin
Catabolite penicillenic acid, penicilloic acid and its polymer, these substances as haptens enter after human body with protein
Or peptide molecule is combined into holoantigen, wherein most importantly Penicilloyl protein, it is to cause most people anaphylactoid
Main cause.Therefore, skin anaphylactic test must be first carried out in clinical application to penicillin medicine, is all China over the years
One of basic nursing routine operation, also clearly stipulate that before injection or oral penicillin class drug in Chinese Pharmacopoeia 2010 editions,
Skin test need to be carried out, the concentration of skin test medical fluid is 500 units/ml, and negative reaction person can use such drug, and during medication
When the lot number of drug has replacement, it is also necessary to reform intracutaneous test.
Data shows reagent for penicillin skin test, and from the benzyl penicillin (PG) of the first generation, the penicilloyl-to the second generation relies more
Propylhomoserin (PLL), mould thiazole carboxylic acid salt (BPNCO), solve allergic reaction, but there are still " false positive is anti-to a certain extent
Answer ", especially infant, false positive rate are up to 10.9% (Li Ya tinkling of pieces of jade " false positive of penicillin skin test 30 analyses " China
Medical Leader .2008.5 (17): 137), to analysis, judging that test results bring very big interference, the reason is that: 1.
The molecular structure of penicillin medicine determines that penicillins aqua is unstable, degradable, failure, the solution for skin test generally newly configured
Want stored refrigerated, validity period was generally within one week, and standing time is too long to be easily decomposed into the allergy such as mould thiazole and penicillenic acid
Substance;And since standing time is too long, repeatedly extract, air bubble pours into back and forth will also result in pollution, especially in summer skin
After examination, easily cause false positive reaction;2. limited by dosage form, need by repeatedly extract, mix gradually be configured to concentration be 500
Unit/ml solution for skin test (States Pharmacopoeia specifications) can use, the preparation method will cause penicillin dissolution it is insufficient, influence skin test knot
The judgement of fruit can obviously increase the false positive rate of test results, delay treatment for infant.
Furthermore the blueness of the different cultivars that circulates on domestic market, different manufacturers, different kinds of process flow, different lot numbers
Mycin drug causes the type and content of contained sensitizer different.For this reason, it may be necessary to develop a kind of more suitable penicillin
Skin test dosage form (traditional reagent for penicillin skin test, mostly injection or suspension injection), to solve the preparation stabilization of existing skin test agent
Property is poor, false positive reaction easily occur, clinical application the disadvantages of there are security risks.
The Chinese invention patent of Publication No. CN 103861125A provides novel penicillin skin test freeze dried powder and system
For technique, penicillin sodium salt 1000-10000 unit, preparation process are mainly contained in every bottle or every of skin test freeze dried powder
Be by the way that bulk pharmaceutical chemicals penicillin sodium salt is diluted with water for injection after, add the excipient of special ratios, pass through the work of optimization
Freeze dried powder is made in skill.When clinical use, a certain amount of physiological saline only need to be injected, is mixed, can be configured to concentration is 500 single
The solution for skin test of position/ml.The skin test freeze dried powder that the patent provides has preparation stability compared to traditional medical skin test agent
Well, the advantages of reducing false positive rate, be a kind of drug that traditional skin test injection is substituted with penicillins skin test freeze dried powder
Developing thought, but disadvantage is that: the related substance-measuring of skin test freeze dried powder, assay are not directed in patent
Method, and in preparation production, the content in relation to substance how is fast and accurately detected, is controlled in drug standards range
It is interior, there is very important effect safely to the industrialization and clinical application of penicillin skin test freeze dried powder.
Regrettably, the quality of penicillins skin test freeze dried powder is not yet included in " Chinese Pharmacopoeia " (2015 editions)
Detection method, pharmacopeia only provide the detection method of Benzylpenicillin sodium salt and benzylpenicillin sodium for injection, chromatographic condition are as follows: chromatographic column:
C18Column;Mobile phase A: potassium dihydrogen phosphate-methanol (72:14), Mobile phase B: acetonitrile, mobile phase A: Mobile phase B=86.5:13.5;
Flow velocity: 1mL/min;Detection wavelength: 225nm, isocratic elution.Official method is applied to Benzylpenicillin sodium salt skin test freeze-dried powder by inventor
When the quality testing of agent, there are following technological deficiencies for discovery: 1. use official method, the main peak retention time of chromatographic compared with
Short, auxiliary material peak has that overlapping, separating degree is poor with impurity peaks, and integral has interference;2. the detection architecture stability of official method is bad, inspection
Result poor reproducibility is surveyed, does not have stability indicative function.
Inventor is retrieved, and discovery is related to reagent for penicillin skin test quality testing, and pertinent literature is as follows:
Document " content of polarimetry measurement penicillin skin test injection " (Ni Hong brightness China medicine company .2008.17 (23):
33) in, a kind of content assaying method of penicillin skin test injection is disclosed, Benzylpenicillin sodium salt is measured using Polarimetry.
Document " two methods of the check experiments of benzylpenicillin skin-test solution the assay " (capital Li Cheng medicine .20007
(2) :), it discloses and carries out assay with iodimetric titration and ultraviolet spectrophotometry.
Document " stability for investigating penicillin skin test agent content " (Heilungkiang Yuan Bo, Zhang Lin, Yuan Ling medicine .2003 (1):
28-29), it discloses and assay, chromatostrip is carried out to the novocillin in reagent for penicillin skin test with high performance liquid chromatography
Part are as follows: chromatographic column: Nova-pak C18Column (3.9mm × 150nm);Mobile phase: 0.05mol/L potassium dihydrogen phosphate-acetonitrile (4:1);
Flow velocity: 1mL/min;Detection wavelength: 230nm;Detector scanning range: 200nm~250nm.Document discovery: skin test agent is to freeze
When dry injection, because of the difference of preparation process, cause the poor stability of preparation, type of impurity and content also more than injection, no
Conducive to detection.
Document " content of high effective liquid chromatography for measuring benzylpenicillin skin-test solution " (Fan Yifeng, Ji Weirong medicine Leader
.2004 23 (12): 952-953), disclose a kind of content with high effective liquid chromatography for measuring benzylpenicillin skin-test solution, chromatography
Condition are as follows: chromatographic column: Eclipse × OB C8Column (4.6mm × 150nm);Mobile phase: methanol: water=40:60;Flow velocity:
1.0mL/min;Detection wavelength: 240nm;Sample volume: 20 μ L.Document discovery: the benzylpenicillin skin-test solution sample of hospital-made is pressed
Effect is undesirable when official method progress assay, and main peak cannot be separated with impurity peaks, only under the conditions of specific mobile phase
Separating degree could be improved, the preferable content for measuring benzylpenicillin skin-test solution.
Document " experimental study of different manufacturers reagent for penicillin skin test quality " (Liang Wei Colleges Of Traditional Chinese Medicine Of Guangxi journal .2000
(4): 61-63 the assay of the reagent for penicillin skin test to different manufacturers production), is disclosed, chromatographic condition are as follows: chromatographic column:
NP C8Column (4.6mm × 180nm);Mobile phase: acetonitrile: sodium dihydrogen phosphate=1:4;Flow velocity: 1.2mL/min;Detection wavelength:
230nm;It was found that the reagent for penicillin skin test quality difference of different manufacturers production is larger, impurity content is a lot of.
From the foregoing, it will be observed that presently commercially available, hospital-made reagent for penicillin skin test is mostly injection, rare freeze dried powder, and:
1. freeze dried powder there is no accurate quality inspection standard, the quality determining method of injection can only be used for reference to improve;2. freeze-dried powder
Agent is compared with injection, and auxiliary material is different, and preparation process is also different, and the requirement of lyophilized preparation stability control is higher, the kind of impurity
Class is also more, therefore the method for constructing the related substance-measuring and assay of freeze dried powder, technical difficulty are higher;3. different factories
Family, Different Preparation are affected for the quality of penicillin skin test freeze dried powder, therefore existing quality determining method is logical
With property is poor, sensitivity is low, it is unfavorable for product Quality Control, considerably increases the risk of clinical application safety.
In conclusion how a kind of quality determining method of penicillin skin test freeze dried powder is provided, it can efficiently, sensitively
Content is measured, the quality control level of said preparation is improved, is those skilled in the art's technical problem urgently to be solved.
Summary of the invention
It is an object of that present invention to provide a kind of quality determining methods suitable for penicillin skin test freeze dried powder, by changing
Into official method, main peak, auxiliary material peak and impurity peaks in penicillin skin test freeze dried powder are clearly separated, sample size
Can precise determination, substantially increase the quality control level of skin test freeze dried powder, solve it is of the existing technology it is above-mentioned lack
It falls into.
Penicillin skin test freeze dried powder of the present invention, be for the exclusive product of certain domestic pharmacy corporation, the prescription by
Benzylpenicillin sodium salt or its salt, excipient and water for injection composition, wherein Benzylpenicillin sodium salt is the solid Benzylpenicillin sodium salt of >=160 units, is assigned
Shape agent is made of lactose and mannitol, and weight ratio is lactose: mannitol=1:3.
Penicillin skin test freeze dried powder of the present invention, preparation process are as follows: the Benzylpenicillin sodium salt or its salt of recipe quantity are taken,
Filling, which is penetrated, to be diluted with water, and along with the excipient for stating recipe quantity, is mixed into medical fluid, medical fluid is through filtering with microporous membrane degerming, packing
Afterwards, be freeze-dried, sealing, packing to get.Wherein, the technique (i.e. lyophilized technique) of freeze-drying specifically comprises the following steps:
(1) it is pre-chilled: the sample after packing being placed in freeze-drying mechanical goods room plate floor, when sample temperature is down to -45 DEG C
When, pressure is 10~30Pa, keeps 3h;Temperature is down to -55 DEG C, and pressure is 10~20Pa, keeps 2h;
(2) it distils: after sample fully charge, starting to vacuumize, temperature keeps 2h, when product room plate floor temperature to -30 DEG C
- 10 DEG C are risen to, 4h is kept;Again when temperature rises to 0 DEG C, 2h is kept;
(3) dry: to keep vacuum state, temperature rises to 40 DEG C, keeps 4h, and freeze-drying terminates;Packing is produced
(4) dispense: in 100 grades of 10000 grades of clean areas, part clean areas, 22 DEG C of temperature, relative humidity 45% carries out nothing
Bacterium packing, tamponade, loading amount ± 3%;
(5) product to be checked is made in labeling, mounted box and vanning.
A kind of quality determining method of penicillin skin test freeze dried powder provided by the invention, technical solution are specific as follows:
A kind of quality determining method of penicillin skin test freeze dried powder, includes the following steps:
(1) preparation of reference substance solution
Precision weighs Benzylpenicillin sodium salt standard items 0.02g, dissolves constant volume with acetonitrile, and miscible, being made into concentration is 0.2~2mg/ml
Solution, be stored in Brown Glass Brown glass bottles and jars only, and under the conditions of 2~8 DEG C place save;
(2) preparation of test solution
Penicillin skin test freeze dried powder 0.2g is taken, it is accurately weighed, it is placed in measuring bottle in right amount, acetonitrile is added to dissolve fine powder, it is fixed
Hold to 2ml, shake up, filters, take subsequent filtrate as test solution;
(3) high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min;
Chromatographic condition:
Stationary phase are as follows: using octadecylsilane chemically bonded silica as the chromatographic column of filler;Mobile phase are as follows: methanol, acetonitrile, water
Mixed liquor, Detection wavelength are as follows: 225~240nm;Flow velocity are as follows: 0.5~1.5mL/min;Column temperature are as follows: 25~35 DEG C;Sample volume are as follows:
20μl;Isocratic elution.
Preferably, in step (1), the reference substance solution concentration being made into is 2mg/ml.
Preferably, in the chromatographic condition of step (3), stationary phase are as follows: Nova-pak C18Chromatographic column.
Preferably, in the chromatographic condition of step (3), mobile phase are as follows: volume ratio=(55~70) of methanol, acetonitrile, water: (5
~20): 25.
It is furthermore preferred that in the chromatographic condition of step (3), the volume ratio of each solvent of mobile phase are as follows: methanol: acetonitrile: water=63:
12:25。
Preferably, in the chromatographic condition of step (3), Detection wavelength are as follows: 235nm.
Preferably, in the chromatographic condition of step (3), flow velocity are as follows: 1.0mL/min.
Preferably, in the chromatographic condition of step (3), column temperature are as follows: 30 DEG C.
Preferably, in step (3), the area of test solution Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak face
Product, deviation are no more than 1.0%.
Benzylpenicillin sodium salt skin test freeze dried powder quality determining method provided by the invention has as follows beneficial to effect:
(1) method specificity is strong, is exclusively used in the quality testing of penicillin drug skin test freeze dried powder, can extend penicillin
Retention time of the main peak in chromatography checking system eliminates interference of the auxiliary material to detection well;So that assay is more acurrate;
(2) method favorable reproducibility carries out reproducibility by this method to the penicillin skin test freeze dried powder sample of different batches
Experimental verification repeats sample introduction 6 times, and peak area RSD is 0.27%;
(3) separating degree is high, testing result is accurate, comprehensively considered chromatographic column, the dicyandiamide solution of mobile phase, Detection wavelength,
The factors such as flow velocity, column temperature change the influence for testing result, shorten chromatography checking system equilibration time, improve the resistance to of chromatographic column
With property, the quality of drug of the present invention can be controlled well, and avoiding harmful substance from being not detected may be to patient clinical drug safety band
The hidden danger come;
(4) availability of sample source is strong, and detection method provided by the invention is easy to operate, versatile, removes mould
Outside plain sodium skin test freeze dried powder, (such as benzylpenicillin potassium, bristopen, piperazine are drawn other penicillin drug skin test freeze dried powders
XiLin sodium, sulbenicillin sodium, ampicillin sodium skin test freeze dried powder), this method can also be used for reference.
Detailed description of the invention
Fig. 1 is the chromatogram that test sample content is measured under the conditions of different chromatographic columns.
Fig. 2 is the chromatogram that test sample content is measured under the conditions of different mobile phases.
Each serial number meaning in Fig. 1 and Fig. 2: 1. Benzylpenicillin sodium salts, 2. lactose, 3. mannitol.
Specific embodiment
The following is specific embodiments of the present invention, is further described to technical solution of the present invention, but of the invention
Protection scope include but is not limited to these embodiments.It is all to include without departing substantially from the change of present inventive concept or equivalent substitute
Within protection scope of the present invention.
Embodiment 1:
Experimental material:
Instrument: 1100 liquid chromatograph of Agilent
Reagent: methanol, acetonitrile (analysis is pure, 500g/ bottles, the production of Hunan Normal University chemical reagent);Ultrapure water, certainly by laboratory
System.
Chromatographic column: Nova-pak C18(5 μm, 3.9mm × 150nm, column number is 0124977) for column
Experimental method:
(1) precision weighs Benzylpenicillin sodium salt standard items 0.02g, dissolves constant volume with acetonitrile, and miscible, being made into concentration is 2mg/ml's
Solution is stored in Brown Glass Brown glass bottles and jars only, and is placed and saved under the conditions of 2~8 DEG C;
(2) preparation of test solution
Penicillin skin test freeze dried powder 0.2g is taken, it is accurately weighed, it is placed in measuring bottle in right amount, acetonitrile is added to dissolve fine powder, it is fixed
Hold to 2ml, shake up, filters, take subsequent filtrate as test solution;
(3) high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition are as follows:
Stationary phase: Nova-pak C18Column, mobile phase: methanol: acetonitrile: water=63:12:25, Detection wavelength: 235nm, stream
Speed: 1.0ml/min, column temperature: 30 DEG C, sample volume: 20 μ l, isocratic elution.
(4) range of linearity: taking Benzylpenicillin sodium salt reference substance, sodium solution is diluted to scale respectively, shakes up, respectively sample introduction, repeats 3
It is secondary, peak area (indicating with trap A) is measured by above-mentioned chromatographic condition, concentration (C) returns average peak area, obtains regression equation
For A=2.563C+0.16452 (r=0.9998), the range of linearity is 120~600 μ g/ml.
(5) precision test: taking above-mentioned 20 μ L of reference substance solution sample introduction, be repeated 6 times, and measures penicillin main peak area, surveys
Calculating gained peak area RSD is 0.2% and 0.3% (n=6).
(6) reappearance test: take same sample lots in step (8) (i.e. lot number be respectively 20150521,20150526,
20150612 sample), the method under item is measured with sample size, is repeated sample introduction 6 times, peak area RSD is 0.27%.
(7) stability test: taking concentration is 0.1mg/ml reference substance solution, by corresponding chromatographic condition respectively the 0th, 2,4,
6, sample introduction measurement in 8,24 hours, peak area RSD is respectively 0.3%, 0.2%, shows that two kinds of solution are stable in 24 hours, and
Sample introduction reproducibility is good.
(8) sample size measures: taking 20 μ L of benzylpenicillin skin-test solution sample direct injected to measure, presses regression equation with peak area
It calculates, the results showed that the content of the benzylpenicillin skin-test solution of lot number 20150521,20150526,20150612 is respectively
97.71%, 99.33%, 98.59%.
2 chromatographic column of embodiment is investigated
1. the preparation of reference substance solution
Precision weighs Benzylpenicillin sodium salt standard items 0.02g, dissolves constant volume with acetonitrile, and miscible, being made into concentration is the molten of 2mg/ml
Liquid is stored in Brown Glass Brown glass bottles and jars only, and is placed and saved under the conditions of 2~8 DEG C;
2. the preparation of test solution
Penicillin skin test freeze dried powder 0.2g is taken, it is accurately weighed, it is placed in measuring bottle in right amount, acetonitrile is added to dissolve fine powder, it is fixed
Hold to 2ml, shake up, filters, take subsequent filtrate as test solution;
3. high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition: following chromatographic column is selected to be compared:
1#:Nova pak C18Column (5 μm, 3.9mm × 150nm);
2#:Eclipse OB C8Column (5 μm, 4.6mm × 150nm);
3#:Agilent Tc C18Column (5 μm, 250 × 4.6mm),
Meanwhile mobile phase is methanol-acetonitrile-water of designated volume ratio;Detection wavelength are as follows: 235nm;Column temperature are as follows: 30 DEG C;Stream
Speed are as follows: 1.0mL/min;Sample volume are as follows: 20 μ l;Isocratic elution.
Testing result is shown in Tables 1 and 2, the chromatogram the result is shown in Figure 1 of different chromatographic columns.
The comparison of the different chromatographic column measurement test sample content results of table 1
Serial number | Title | Appearance time (min) | The rate of recovery (%) | RSD (%) |
1# | Nova pak C18Column | 4.58 | 99.8 | 1.1 |
2# | Eclipse OB C8Column | 3.48 | 98.7 | 1.5 |
3# | Agilent Tc C18Column | 3.15 | 95.6 | 0.9 |
The different chromatographic columns of table 2 measure test sample content
Ingredient (%) | Nova-pak C18Column | Eclipse OB C8Column | Agilent Tc C18Column |
Reference substance | 99.1 | 92.5 | 87.4 |
Benzylpenicillin sodium salt | 96.4 | 94.3 | 80.9 |
Lactose | 2.6 | 3.1 | 0.12 |
Mannitol | 1.4 | 2.2 | 0.44 |
Conclusion: when high effective liquid chromatography for measuring reagent for penicillin skin test freeze-dried powder, being measured using different chromatographic columns,
Nova-pak C18Column 4min or so appearance, minute 5min or so, sample minute are short;Using Eclipse OB C8
Column, 7min or so appearance, minute 10min or so, sample minute are long;Using Agilent Tc-C18 column, 3min is left
Right appearance, minute 5min or so.But both rear (i.e. the chromatographic column of 2# and 3#) cannot preferably separate each principal component peak,
Auxiliary material peak and impurity peaks cause data inaccurate.And use Nova-pak C18Column, minute is short, each peak good separating effect,
It is high-efficient, it is suitble to high-volume to examine, is worth of widely use.
3 mobile phase of embodiment is investigated
1. the preparation of reference substance solution, method is referring to embodiment 1.
2. the preparation of test solution, method is referring to embodiment 1.
3. high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition: following flow visualizing is selected to be compared:
1#: methanol: water, volume ratio are respectively 75:25,78:22,80:20;
2#: methanol: acetonitrile: water, volume ratio are respectively 55:20:25,63:12:25,70:5:25;
3#: methanol: 0.2% glacial acetic acid aqueous solution, volume ratio are respectively 75:25,78:22,80:20;
4#: acetonitrile: 0.2% glacial acetic acid aqueous solution, volume ratio are respectively 75:25,78:22,80:20;
Meanwhile chromatographic column are as follows: Nova-pak C18Column (5 μm, 3.9mm × 150nm), Detection wavelength are as follows: 235nm;Column temperature
Are as follows: 30 DEG C;Flow velocity are as follows: 1.0mL/min;Sample volume are as follows: 20 μ l;Isocratic elution.
Testing result is shown in Table 3, and the chromatogram result of different flow visualizings is shown in Fig. 2.
The retention time at each peak in the different flow visualizings of table 3
Conclusion: 1. 1#, 3# and 4# are the methanol-water of different proportion, -0.2% glacial acetic acid aqueous solution of methanol, acetonitrile-respectively
0.2% glacial acetic acid aqueous solution uses 1#, 3# or 4# flow visualizing as flow visualizing, discovery, and the elution of test sample is unknown
Aobvious, separating degree is poor;And methanol-acetonitrile-water (i.e. 2#) of different proportion is used to be used as flow visualizing, it is suitable to the appearance of test sample
Sequence and retention time are all better than 1#, 3# and 4# system, and each peak shape is concentrated, and separating effect is significant, and retention time is longer, meets inspection
It surveys and requires, therefore using 2# system as ideal flow phase of the invention.2. by the comparison of standard deviation, discovery: when methanol-second
When nitrile-water volume ratio is 63:12:25, detection effect is best.
4 flow velocity of embodiment is investigated
1. the preparation of reference substance solution, method is referring to embodiment 1.
2. the preparation of test solution, method is referring to embodiment 1.
3. high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition:
Chromatographic column are as follows: Nova-pak C18Column (5 μm, 3.9mm × 150nm);Mobile phase is methanol-second of designated volume ratio
Nitrile-water;Detection wavelength are as follows: 235nm;Column temperature are as follows: 30 DEG C;Sample volume are as follows: 20 μ l;Isocratic elution, investigating flow velocity is respectively
To the influence of high performance liquid chromatography detection when 0.5ml/min, 1.0ml/min and 1.5ml/min.
Conclusion: when 1. flow velocity is respectively 0.5ml/min, 1.0ml/min and 1.5ml/min, testing result difference is little, because
Optional 0.5~the 1.5ml/min of this flow rates;2. chromatographic peak is slightly wide when flow velocity is 0.5ml/min;When flow velocity is 1.5ml/
When min, appearance is slightly fast, so that the acquisition of detection data slightly has deviation;And it is best when flow velocity is 1.0ml/min, it can be accurate
Acquire data, therefore the optional 1.0ml/min of optimum flow rate.
The influence of 5 column temperature of embodiment
1. the preparation of reference substance solution, method is referring to embodiment 1.
2. the preparation of test solution, method is referring to embodiment 1.
3. high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition:
Chromatographic column are as follows: Nova-pak C18Column (5 μm, 3.9mm × 150nm);Mobile phase is methanol-second of designated volume ratio
Nitrile-water;Detection wavelength are as follows: 235nm;Flow velocity are as follows: 1.0ml/min;Sample volume are as follows: 20 μ l;Isocratic elution, investigating column temperature is respectively
Influence at 25 DEG C, 28 DEG C, 30 DEG C and 35 DEG C to high performance liquid chromatography detection.Testing result is shown in Table 4.
Chromatographic behavior under the different column temperatures of table 4 compares
Conclusion: when 1. column temperature is respectively 25 DEG C, 28 DEG C, 30 DEG C and 35 DEG C, the difference of assay result is little, therefore column
Optional 25~35 DEG C of warm range;2. discovery column pressure is slightly higher, and main peak is wider, so that theoretical cam curve when column temperature is 25 DEG C, 28 DEG C
It reduces, so separating degree is slightly lower;And when column temperature is 30 DEG C, separating degree highest illustrates that separating effect is best, therefore optimum column temperature
Optional 30 DEG C.
The selection of the measurement wavelength of embodiment 6
1. the preparation of reference substance solution, method is referring to embodiment 1.
2. the preparation of test solution, method is referring to embodiment 1.
3. high performance liquid chromatography detection
Accurate absorption reference substance solution, test solution injection liquid chromatograph, record chromatogram, record time are respectively
0~20min, in test solution, the area of Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area (1.0%);
Chromatographic condition:
Chromatographic column are as follows: Nova-pak C18Column (5 μm, 3.9mm × 150nm);Mobile phase is methanol-second of designated volume ratio
Nitrile-water;Flow velocity are as follows: 1.0ml/min;Sample volume are as follows: 20 μ l;Isocratic elution, investigate Detection wavelength be respectively 225nm, 235nm and
To the influence of high performance liquid chromatography detection when 240nm.After carrying out data fitting to testing result, following linear regression side is obtained
Journey:
S225=217.24 ρ+137.08R2=0.9998;
S235=327.87 ρ+364.5R2=0.9998;
S240=129.258 ρ+145.7R2=0.9938;
Conclusion: the degree of fitting for the calibration curve equation established at 235nm wavelength is higher.Testing result shows, in
The main peak area value that test sample is measured under 225nm, 235nm and 240nm wavelength is respectively 223.9,627.8 and 185.5, it is seen that
Absorption at 225 and 240nm wavelength is weaker.So Detection wavelength selects 235nm optimum, at this time penicillin skin test freeze-dried powder
The detection sensitivity highest of agent.
Claims (6)
1. a kind of quality determining method of penicillin skin test freeze dried powder, includes the following steps:
(1) preparation of reference substance solution
Precision weighs Benzylpenicillin sodium salt standard items 0.02g, dissolves constant volume with acetonitrile, and miscible, being made into concentration is the molten of 0.2~2mg/ml
Liquid is stored in Brown Glass Brown glass bottles and jars only, and is placed and saved under the conditions of 2~8 DEG C;
(2) preparation of test solution
Penicillin skin test freeze dried powder 0.2g is taken, it is accurately weighed, it is placed in measuring bottle in right amount, acetonitrile is added to dissolve fine powder, be settled to
2ml shakes up, and filtration takes subsequent filtrate as test solution;
(3) high performance liquid chromatography detection
It is accurate respectively draw reference substance solution, test solution injects liquid chromatograph, records chromatogram, the record time is 0~
20min;
Chromatographic condition:
Stationary phase are as follows: Nova-pak C18Chromatographic column;Mobile phase are as follows: methanol, acetonitrile, water mixed liquor, and methanol, acetonitrile, water
Volume ratio=(55~70): (5~20): 25, Detection wavelength are as follows: 235nm;Flow velocity are as follows: 0.5~1.5mL/min;Column temperature are as follows:
25~35 DEG C;Sample volume are as follows: 20 μ l;Isocratic elution;
The method is for Benzylpenicillin sodium salt, lactose and the mannitol in separating penicillin skin test freeze dried powder.
2. the quality determining method of penicillin skin test freeze dried powder according to claim 1, it is characterised in that: the step
Suddenly in (1), the reference substance solution concentration being made into is 2mg/ml.
3. the quality determining method of penicillin skin test freeze dried powder according to claim 1, it is characterised in that: the step
Suddenly in the chromatographic condition of (3), the volume ratio of each solvent of mobile phase are as follows: methanol: acetonitrile: water=63:12:25.
4. the quality determining method of penicillin skin test freeze dried powder according to claim 1, it is characterised in that: the step
Suddenly in the chromatographic condition of (3), flow velocity are as follows: 1.0mL/min.
5. the quality determining method of penicillin skin test freeze dried powder according to claim 1, it is characterised in that: the step
Suddenly in the chromatographic condition of (3), column temperature are as follows: 30 DEG C.
6. the quality determining method of penicillin skin test freeze dried powder according to claim 1, it is characterised in that: the step
Suddenly in (3), the area of test solution Benzylpenicillin sodium salt main peak must not exceed reference substance solution peak area, and deviation is no more than 1.0%.
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Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5991365A (en) * | 1982-11-17 | 1984-05-26 | Toyo Soda Mfg Co Ltd | Elute composition for liquid chromatograph |
CN103336083A (en) * | 2013-06-19 | 2013-10-02 | 哈尔滨工业大学 | High performance liquid chromatography detection method for penicillin G in penicillin fungi residues |
CN104483427A (en) * | 2014-12-08 | 2015-04-01 | 华东理工大学 | Method for separating, enriching and detecting 12 antibiotics in drinking water source |
CN105628808A (en) * | 2015-12-25 | 2016-06-01 | 光明乳业股份有限公司 | Pretreatment method and detection method of amoxicillin, penicillin G and penicillin V |
-
2016
- 2016-08-31 CN CN201610797234.2A patent/CN106404953B/en active Active
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS5991365A (en) * | 1982-11-17 | 1984-05-26 | Toyo Soda Mfg Co Ltd | Elute composition for liquid chromatograph |
CN103336083A (en) * | 2013-06-19 | 2013-10-02 | 哈尔滨工业大学 | High performance liquid chromatography detection method for penicillin G in penicillin fungi residues |
CN104483427A (en) * | 2014-12-08 | 2015-04-01 | 华东理工大学 | Method for separating, enriching and detecting 12 antibiotics in drinking water source |
CN105628808A (en) * | 2015-12-25 | 2016-06-01 | 光明乳业股份有限公司 | Pretreatment method and detection method of amoxicillin, penicillin G and penicillin V |
Non-Patent Citations (3)
Title |
---|
Separation and Determination of Five Penicillins by Reversed Phase HPLC;I. P. Kaniou et al;《Journal of Liquid Chromatography & Related Technologies》;19931231;第16卷(第13期);2891-2897 |
The Analysis of Penicillins in Biological Fluids and Pharmaceutical Preparations by High Performance Liquid Chromatography: A Review;John O. Miners;《Journal of Liquid Chromatography》;19851231;第8卷(第15期);2827-2843 |
马珊珊 等.加速溶剂萃取(ASE)⁃固相萃取(SPE)⁃高效液相色谱法(HPLC)测定土壤中青霉素钠.《环境化学》.2014,第33卷(第11期), |
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